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Title: Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection
Authors: Gibson, Josie F.
Bojarczuk, Aleksandra
Evans, Robert J.
Kamuyango, Alfred Alinafe
Hotham, Richard
Lagendijk, Anne K.
Hogan, Benjamin M.
Ingham, Philip William
Renshaw, Stephen A.
Johnston, Simon A.
Keywords: Science::Medicine
Issue Date: 2022
Source: Gibson, J. F., Bojarczuk, A., Evans, R. J., Kamuyango, A. A., Hotham, R., Lagendijk, A. K., Hogan, B. M., Ingham, P. W., Renshaw, S. A. & Johnston, S. A. (2022). Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection. PLoS Pathogens, 18(4), e1010389-.
Journal: PLoS Pathogens 
Abstract: Meningitis caused by infectious pathogens is associated with vessel damage and infarct formation, however the physiological cause is often unknown. Cryptococcus neoformans is a human fungal pathogen and causative agent of cryptococcal meningitis, where vascular events are observed in up to 30% of patients, predominantly in severe infection. Therefore, we aimed to investigate how infection may lead to vessel damage and associated pathogen dissemination using a zebrafish model that permitted noninvasive in vivo imaging. We find that cryptococcal cells become trapped within the vasculature (dependent on their size) and proliferate there resulting in vasodilation. Localised cryptococcal growth, originating from a small number of cryptococcal cells in the vasculature was associated with sites of dissemination and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension reporter we identified dissemination from intact blood vessels and where vessel rupture occurred. Finally, we manipulated blood vessel tension via cell junctions and found increased tension resulted in increased dissemination. Our data suggest that global vascular vasodilation occurs following infection, resulting in increased vessel tension which subsequently increases dissemination events, representing a positive feedback loop. Thus, we identify a mechanism for blood vessel damage during cryptococcal infection that may represent a cause of vascular damage and cortical infarction during cryptococcal meningitis.
ISSN: 1553-7366
DOI: 10.1371/journal.ppat.1010389
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Institute of Molecular and Cell Biology (A*Star) Singapore
Rights: © 2022 Gibson et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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